Search

Introduction: Articular cartilage injuries of the knee are a complex and challenging clinical pathology. Objectives: The purpose of this study was to establish consensus statements via a Delphi process on chondrocyte-based cartilage (CBC) approaches and scaffolds for cartilage injury. Methods: A consensus process on knee cartilage injuries utilizing a modified Delphi technique was conducted. Seventy-nine surgeons across 17 countries participated in these consensus statements. Ten questions were generated on chondrocyte-based approaches and scaffolds, with 3 rounds of questionnaires and final voting occurring. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was defined as 100% agreement with a proposed statement. Results: Of the 10 total questions and consensus statements on CBC repair developed from 3 rounds of voting, 1 question achieved unanimous consensus, 6 achieved strong consensus, 2 achieved consensus, and 1 did not achieve consensus. Conclusions: The statements that achieved strong or unanimous consensus were related to indication and relative indications for CBC repair, harvesting site for chondrocytes, differentiating healthy and unhealthy cartilage, sizing defects, minimizing complications, and orthobiologics utility. These consensus statements regarding chondrocyte-based approaches and scaffolds for cartilage injury will hopefully assist clinicians in the management of this challenging pathology.

Abstract Aims Heart failure is an increasingly recognized later stage manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) that can require heart transplantation (HT) to appropriately treat. We aimed to study contemporary ARVC HT outcomes in a national registry. Methods and results The United Network for Organ Sharing registry was queried for HT recipients from 1/1994 through 2/2020. ARVC patients were compared with non‐ARVC dilated, restrictive, and hypertrophic cardiomyopathy HT patients (HT for ischaemic and valvular disease was excluded from analysis). Post‐HT survival was assessed using Kaplan–Meier estimates. A total of 189 of 252 (75%) waitlisted ARVC patients (median age 48 years, 65% male) underwent HT, representing 0.3% of the total 65 559 HT during the study time period. Annual frequency of HT for ARVC increased significantly over time. ARVC patients had less diabetes (5% vs. 17%, P

Copyright of Climacteric is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Females are at greatest risk for reinjury after return to sport (RTS) following anterior cruciate ligament (ACL) reconstruction (ACLR). The reasons for these sex differences, however, remain unclear. Psychological factors such as kinesiophobia have been identified as a potential predictor for reinjury following RTS. Studies investigating kinesiophobia have identified sex differences, yet whether this holds in the ACLR population remains unknown. The purpose of this study was to examine whether there are sex differences in kinesiophobia and other psychological factors, such as readiness to RTS and self-reported pain in the ACLR population. A total of 20 participants, eleven males (23.0 ± 8.4 years, 178.9 ± 7.6 cm, 76.8 ± 10.4 kg) and 9 females (19.6 ± 5.3 years, 165.1 ± 4.0 cm, 73.2 ± 25.0 kg) voluntarily participated in this study. The Tampa Scale for Kinesiophobia (TSK-11), Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scale, and self-reported pain using a visual analog scale (VAS) were administered after clearance for RTS (10.5 ± 2.3 months post-ACLR). Statistical significance was set a priori at p<0.05. A significant difference between sexes was observed for the ACL-RSI with males reporting a significantly higher score (92.82±16.16) compared to females (77.0±15.54; p = 0.040). There were no significant differences between sexes for VAS for pain (males = 4.55 ± 6.50; females = 1.22 ± 3.31; p = 0.228) and TSK-11 (males = 18.73 ± 3.17; females = 19.67 ± 4.61; p = 0.596). The results of this study demonstrated males had significantly higher ACL-RSI scores than females, suggesting males may have higher psychological readiness following clearance for RTS. This study did not demonstrate significant differences between sexes for kinesiophobia or pain level. Caution in interpretation of results is warranted due to the small sample size, highlighting the need for further research in this area. [ABSTRACT FROM AUTHOR]

Background. Liver transplantation (LT) candidates frequently have multiple cardiovascular risk factors, and cardiovascular disease is a major cause of morbidity and mortality after LT. Coronary artery calcium (CAC) scores are a noninvasive assessment of coronary artery disease using computed tomography. This study examines CAC scores and cardiac risk factors and their association with outcomes after LT. Methods. Patients who underwent LT between January 2010 and June 2019 with a pretransplant CAC score were included in this study. Patients were divided by CAC score into 4 groups (CAC score 0, CAC score 1–100, CAC score 101–400, CAC score >400). Major adverse cardiovascular events (MACEs) were defined as myocardial infarction, stroke, revascularization, heart failure, atrial fibrillation, and cardiovascular death. Associations between CAC score and MACE or all-cause mortality within the 5-y post-LT follow-up period were analyzed using Cox regression. Statistical significance was defined as P < 0.05. Results. During the study period, 773 adult patients underwent their first LT, and 227 patients met our study criteria. The median follow-up time was 3.4 (interquartile range 1.9, 5.3) y. After 5 y, death occurred in 47 patients (20.7%) and MACE in 47 patients (20.7%). In multivariable analysis, there was no difference in death between CAC score groups. There was significantly higher risk of MACE in the CAC score >400 group, with a hazard ratio 2.58 (95% confidence interval 1.05, 6.29). Conclusions. CAC score was not associated with all-cause mortality. Patients with CAC score >400 had an increase in MACEs within the 5-y follow-up period compared with patients with a CAC score = 0. Further research with larger cohorts is needed to examine cardiac risk stratification in this vulnerable patient population.

# Background Anterior cruciate ligament (ACL) injury is extremely common among athletes. Rate of second ACL injury due to surgical graft rupture or contralateral limb ACL injury is approximately 15-32%. Psychological readiness to return to sport (RTS) may be an important predictor of successful RTS outcomes. Psychological readiness can be quantified using the ACL Return to Sport after Injury (ACL-RSI) questionnaire, with higher scores demonstrating greater psychological readiness. # Purpose The purpose of this study was to investigate differences in functional performance and psychological readiness to return to sport among athletes who have undergone primary ACL reconstruction (ACLR). # Study Design Descriptive cohort study # Methods Eighteen athletes who had undergone primary ACLR were tested at time of RTS clearance. The cohort was divided into two groups, high score (HS) and low score (LS), based on median ACL-RSI score, and performance on static and dynamic postural stability testing, lower extremity isokinetic and isometric strength testing, and single leg hop testing was compared between the groups using an independent samples t-test. # Results The median ACL-RSI score was 74.17. The average ACL-RSI score was 83.1±6.2 for the HS group and 61.8±8.0 for the LS group. High scorers on the ACL-RSI performed significantly better on isometric knee flexion as measured via handheld dynamometry (22.61% ±6.01 vs. 12.12% ±4.88, p=0.001) than the low score group. # Conclusion The findings suggest that increased knee flexion strength may be important for psychological readiness to RTS after primary ACLR. Further research is indicated to explore this relationship, however, a continued emphasis on improving hamstring strength may be appropriate during rehabilitation following ACLR to positively impact psychological readiness for RTS. # Level of Evidence III

Abstract Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. Results Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. Conclusions Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.

# Purpose There is a high rate of second anterior cruciate ligament (ACL) injury (ipsilateral graft or contralateral ACL) upon return-to-sport (RTS) following ACL reconstruction (ACLR). While a significant amount of epidemiological data exists demonstrating sex differences as risk factors for primary ACL injury, less is known about sex differences as potential risk factors for second ACL injury. The purpose of this study is to determine if there are sex-specific differences in potential risk factors for second ACL injury at the time of clearance for RTS. # Methods Ten male and eight female athletes (age: 20.8 years ±6.3, height: 173.2 cm ±10.1, mass: 76.6 kg ±18.3) participated in the study following ACLR at time of RTS (mean 10.2 months). Performance in lower extremity isokinetic and isometric strength testing, static and dynamic postural stability testing, and a single leg stop-jump task was compared between the sexes. # Results Normalized for body weight, males had significantly greater isokinetic knee flexion (141±14.1 Nm/kg vs. 78±27.4 Nm/kg, p=0.001) and extension strength (216±45.5 Nm/kg vs. 159±53.9 Nm/kg, p=0.013) as well as isometric flexion (21.1±6.87% body weight vs. 12.5±5.57% body weight, p=0.013) and extension (41.1±7.34% body weight vs. 27.3±11.0% body weight, p=0.016) strength compared to females. In the single-leg stop jump task, males had a greater maximum vertical ground reaction force during landing (332±85.5% vs. 259±27.4% body weight, p=0.027) compared to females. # Conclusions Based on these results, there are significant differences between sexes following ACLR at the time of RTS. Lower knee flexion and extension strength may be a potential risk factor for second ACL injury among females. Alternatively, the increased maximum vertical force observed in males may be a potential risk factor of second ACL injury in males. Although these results should be interpreted with some caution, they support that rehabilitation programs in the post-ACLR population should be individualized based on the sex of the individual. # Level of Evidence Level 3

Current treatment of Chlamydia trachomatis using doxycycline and azithromycin introduces detrimental side effects on the host’s microbiota. As a potential alternative treatment, the myxobacterial natural product sorangicin A (SorA) blocks the bacterial RNA polymerase. In this study we analyzed the effectiveness of SorA against C. trachomatis in cell culture, and explanted fallopian tubes and systemic and local treatment in mice, providing also pharmacokinetic data on SorA. Potential side effects of SorA on the vaginal and gut microbiome were assessed in mice and against human-derived Lactobacillus species. SorA showed minimal inhibitory concentrations of 80 ng/mL (normoxia) to 120 ng/mL (hypoxia) against C. trachomatis in vitro and was eradicating C. trachomatis at a concentration of 1 µg/mL from fallopian tubes. In vivo, SorA reduced chlamydial shedding by more than 100-fold within the first days of infection by topical application corresponding with vaginal detection of SorA only upon topical treatment, but not after systemic application. SorA changed gut microbial composition during intraperitoneal application only and did neither alter the vaginal microbiota in mice nor affect growth of human-derived lactobacilli. Additional dose escalations and/or pharmaceutical modifications will be needed to optimize application of SorA and to reach sufficient anti-chlamydial activity in vivo.

We report a case of a woman with arrhythmogenic right ventricular cardiomyopathy (ARVC) who presented with severe right-sided heart failure and cardiac cirrhosis that mandated heart-liver transplantation. This case highlights an emerging sex-based difference in ARVC where female sex is associated with a higher risk of heart failure than in male patients with ARVC. (Level of Difficulty: Advanced.)

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported.

Summary: The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women. Key Words: breastfeeding, immune activation, peripartum cardiomyopathy

In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of Dentipellis fragilis, which were named dentifragilins A–H. In addition, the known cyathane derivatives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Several of the compounds exhibited significant activities in standardized cell-based assays for the determination of antimicrobial and cytotoxic effects. The discovery of cyathanes in the genus Dentipellis has chemotaxonomic implications, as this class of diterpenoids has already been shown to be characteristic for mycelial cultures of the related genera Hericium and Laxitextum, which are classified as Dentipellis in the family Hericiaceae.

Undergraduate research is an excellent example of student engagement that leads to numerous benefits for the student and faculty. However, for students to gain the most from the experience, high-quality mentorship is needed. This article will introduce the readers to the Salient Practices Framework which is based on a comprehensive review of the research on undergraduate research mentorship. This article will outline how a group of faculty adapted the Salient Practices Framework to the virtual environment that resulted from COVID-19. Lessons learned from initial efforts to mentoring in the virtual environment will also be discussed. Implementation of mentoring in a virtual context opens up opportunities for increased access and broadening of research teams and mentoring constellations.

BackgroundThe Equitest system (Neurocom) is a computerized dynamic posturography device used by health care providers and clinical researchers to safely test an individual’s postural control. While the Equitest system has evaluative and rehabilitative value, it may be limited owing to its cost, lack of portability, and reliance on only sagittal plane movements. Virtual reality (VR) provides an opportunity to reduce these limitations by providing more mobile and cost-effective tools while also observing a wider array of postural characteristics. ObjectiveThis study aimed to test the plausibility of using VR as a feasible alternative to the Equitest system for conducting a sensory organization test. MethodsA convenience sample of 20 college-aged healthy individuals participated in the study. Participants completed the sensory organization test using the Equitest system as well as using a VR environment while standing atop a force plate (Bertec Inc). The Equitest system measures the equilibrium index. During VR trials, the estimated equilibrium index, 95% ellipse area, path length, and anterior-posterior detrended fluctuation analysis scaling exponent alpha were calculated from center of pressure data. Pearson correlation coefficients were used to assess the relationship between the equilibrium index and center of pressure–derived balance measures. Intraclass correlations for absolute agreement and consistency were calculated to compare the equilibrium index and estimated equilibrium index. ResultsIntraclass correlations demonstrated moderate consistency and absolute agreement (0.5 < intraclass correlation coefficient < 0.75) between the equilibrium index and estimated equilibrium index from the Equitest and VR sensory organization test (SOT), respectively, in four of six tested conditions. Additionally, weak to moderate correlations between force plate measurements and the equilibrium index were noted in several of the conditions. ConclusionsThis research demonstrated the plausibility of using VR as an alternative method to conduct the SOT. Ongoing development and testing of virtual environments are necessary before employing the technology as a replacement to current clinical tests.

Abstract Background Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination. Results The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here. Conclusions We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.